Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures.

Method: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD Surveillance Unit over a 15 year period to identify Heidenhain cases.

Results: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of the prion protein gene.

Conclusions: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties. Because ocular intervention carries with it the risk of onward transmission awareness of this condition among ophthalmologists is important.

Washington, DC, Nov. 18 (UPI) -- A New York man who died from a rarebrain disorder similar to mad cow disease in May underwent an eyeprocedure prior to his death that raises concerns about the possibilityof transmitting the fatal disease to others, United Press Internationalhas learned.

The development comes on the heels of the announcement Thursday by U.S.Department of Agriculture officials of a possible second case of mad cowdisease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from CreutzfeldtJakob disease, an incurable brain-wasting illness that strikes about oneperson per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for theeye disease glaucoma in 2003, approximately a year before his death. Theprocedure involves the use of a tonometer, which contacts the cornea --an eye tissue that can contain prions, the infectious agent thought tocause CJD.

Ann Marie's concern is that others who had the tonometer used on themcould have gotten infected.

A 2003 study by British researchers suggests her concerns may bejustified. A team led by J.W. Ironside from the NationalCreutzfeldt-Jakob Disease Surveillance Unit at the University ofEdinburgh examined tonometer heads and found they can retain corneatissue that could infect other people -- even after cleaning anddecontaminating the instrument.

"Retained corneal epithelial cells, following the standarddecontamination routine of tonometer prisms, may represent potentialprion infectivity," the researchers wrote in the British Journal ofOphthalmology last year. "Once the infectious agent is on the cornea, itcould theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD andsimilar diseases, are notoriously difficult to destroy and are capableof withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief ofsurgery in the neuropathology department at Yale University, agreed withthe British researchers that tonometers represent a potential risk ofpassing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks ofcorneas since 1977 when her own study, published in the New EnglandJournal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a yearbefore he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Departmentof Health, noted in a 2001 report that procedures involving the corneaare considered medium risk for transmitting CJD. The first two patientswho have a contaminated eye instrument used on them have the highestrisk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusingequipment that came in contact with patients' eyes out of concern itcould result in the transmission of variant CJD, the form of the diseasehumans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases ofCJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, butconcerns about the cattle illness in the United States could increase inlight of the USDA announcement Thursday that a cow tested positive oninitial tests for the disease. If confirmed, this would be the secondU.S. case of the illness; the first was detected in a Washington cowlast December. The USDA said the suspect animal disclosed Thursday didnot enter the food chain. The USDA did not release further details aboutthe cow, but said results from further lab tests to confirm the initialtests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department andlater the eye doctor who performed the procedure about her husband'sillness and her concerns about the risk of transmitting CJD via thetonometer.

The optometrist -- whom she declined to name because she did not want tojeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (thehealth department) back and they didn't seem concerned about it," sheadded. "I just kept getting angrier and angrier when I felt I was beingdismissed."

She said the state health department "seems to have an attitude of don'task, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're soafraid the public will panic? I don't know, but I don't think that theanswer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPIshe would look into whether the agency was concerned about thepossibility of transmitting CJD via tonometers, but she had not calledback prior to story publication.

Disposable tonometers are readily available and could avoid the risk oftransmitting the disease, Ironside and colleagues noted in their study.Ann Marie Da Silva said she asked the optometrist whether he useddisposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come intocontact with the cornea and could represent a source of infection asthey are either difficult to decontaminate or cannot withstand the harshprocedures necessary to inactivate prions. These include corneal burrs,diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called HeidenhainVariant, told UPI health officials were not doing enough to preventpeople from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simplyaren't doing it," said Singletary, who is a member of CJD Watch and CJDVoice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman ChristinePearson did not return a phone call from UPI seeking comment. Theagency's Web site states the eye is one of three tissues, along with thebrain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJDthrough contaminated surgical instruments and tissue transplants. Thisincludes as many as four who were infected by corneal grafts. The agencynoted no such cases have been reported since 1976, when sterilizationprocedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfectionprocedures used on optical instruments, such as tonometers, fail. Theywrote their finding of cornea tissue on tonometers indicates that "nocurrent cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infectedequipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in thismanner, he said, because CJD cases often aren't investigated and theagency has not required physicians nationwide report all cases of CJD.

"There's no national surveillance unit for CJD in the United States;people are dying who aren't autopsied, the CDC has no way of knowing"whether people have been infected via infected equipment or tissues, hesaid.

Ann Marie Da Silva said she has contacted several members of her state'scongressional delegation about her concerns, including Rep. Sue Kelly,R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I alsowant more of a dialogue going on with the public and the healthdepartment," she said.

Copyright 2004 United Press International

http://www.washtimes.com/upi-breaking/20041118-030642-2974r.htm

The Eyes have it/CJD * and they could be stealing them from YOUR loved one, hence the spread of CJD (aka MADCOW DISEASE) will spread...

This document accompanying this transmission containsconfidential information belonging to the sender that is legallyprivileged. This information is intended only for the use of theindividual or entry names above. If you are not the intended recipient,you are hereby notified that any disclosure, copying distribution, orthe taking of any action in reliances on the contents of this telefaxedinformation is strictly prohibited. If you received this telefax in error, please notify us by tlephone immediately to arrange for return of the original documents.--------------------------Patient Account: 90000014-518Med. Rec. No.: (0160)118511QPatient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

MICROSCOPIC DESCRIPTION:The spongiform change is evident in all areas of neocortex, varyingfrom mild to moderate in severity with only very mild neuronal loss andgliosis. In the bilateral occipital lobes, there is severe loss cortical neurons and gliosis, with a corresondinq pallor of theunderlying white matter. There is only minimal, focal spongiform changein corpus striatum, lentiform nuclei, thalamus, hippocampus, brainstemand cerebellum. There is no significant loss of neurons from the lateralgeniculate nucleus, and the optic chiasm and tracts are well-myelinated.

COMMENTS; See also western blot report from Dr. Gambetti's labAmyloid stains are not completed for this case as of this date. The results, which are not essential for the diagnosis, will be reportedseparately in an addendum.

(this was hand written notes)no anyloid evident in the special stains.no evidence of paques.

CLINICAL HISTORYThis patient was a 63-year-old white female with recent onset of progressive dementia. She was well until September of this year, when she noted a decrease in her visual activity and was found to have visualfield defets as well. MRI revealed no lesions in the orbits or optic pathways. She was admitted to the hospital with the working diagnosisof bilateral optic neuropathy for a course of intravenous methylprednisolone, but her vision continued to deteriorate. She developed increasing memory and speech impairment, weakness and myoclonus. She died on 12/14/97, approximately three and one-halfmonths after her symptoms started.

GROSS DESCRIPTION:Submitted are the brain, convexity dura and pituitary gland.

The pituitary gland is very dark and almost hemorrhagic in appearance,but has no obvious hematoma. It is submitted totally for histology.

The right convexity dura has diffuse but minimal subdura hemorrhage,and the dura is otherwize unremarkable.

The brain is normally developed with normal size for an adult and issymmetric externally. It does not have apparent sulcal widening. Thereis mild congestion of thc leptomeninges, which are transparent. There isno evidence of inflammatory exudete. There is no evidence of internalsoftenings or other lesions externally. The cerebral arteries have focalatherosclerosis, but are without significant compromise of the vesselslumens. There im no evidence of aneurysms or malformations.

The hemispheres are sliced coronally revealing, a ventricular systemwhich is mildly enlarged. The cortical ribbon is normal in thicknessthrouqhout most of the brain, except for the inferior amd medialoccipital lobes bilaterally, where the cortex is firm, thin and has abrownish discoloration, more severely so on the left than the right. Inaddition there is a spherical enlargement of the left occipital horn ofthe lateral ventricle which communicates with the remainder of thelateral ventricle. Tho tissue of the white matter around thisenlargement is somewhat softer then in other areas. Other areas of thebrain are grossly unremarkable. The brainstem and cerebellum are slicedtransversely, revealing normal development and no evidence of grosschanges or lesions.

This is a 63-year-old white female with a recent onset of progressivedementia. Her past medical history is significant for hypothyroidism.She was well until September of this year, when she noted visualdifficulty. By mid-October, she could not read the newspaper. She was found to have a decrease in visual acuity and visual field defects. One week after her initial evaluation, a panel of blood tests showed no significant abnormalities and a MRI revealed some periventricular white matter "plaque-like" areas but no lesions in the orbits or optic pathways.

The patient had continued deterioration and distortion of her vision.The visual field defects increased, and she was found to have paracentral scotomas which were thought to be consistent with bilateral optic neuropathy. Early in November, she was admitted to the hospital for a course of intravenous methyl prednisolone.

During her hospital stay, she was noted to have short term memory andspeech impairment; her vision did not improve. She was discharged withthe diagnosis of Creutzfeldt-Jakob disease.

Later, the patient developed progressive dementia with markedimpairment of speech and memory. She had complete visual loss, increased weakness and myoclonus. She died on December 14, 1997.

EXTERNAL EXAMINATION: The body is that of a 63-year-old well-nourished,well-developed white female. There is no rigor mortis present, and thereis unfixed dependent lividity on the posterior surface. The head isnormocephalic with a moderate amount of gray, medium length scalp hair.The irides are blue with equal pupils measuring 0.4 mm in diameter. Thenares are patent with no exudate. Dentition is fair. Buccal membranesare normal. There is normal female hair distribution. The chest does nothave increased anterior-posterior diameter. The abdomen is slightlyprotuberant. Lymph node enlargement is not present. The extremities areunremarkable. The genitalia are those of a normal female. Twowell-healed remote scars are identified in the abdomen: one in the rightupper quadrant and another in the superpubic area.

BRAIN: The brain weighs 1450 gm. The gyri and sulci display a normalpattern without edema or atrophy. The meninges show no abnormalities.The circle of Willis, basilar and vertebral arteries show no significantatherosclerosis. The brain is fixed in formalin for later examination bya neuropathologist (see neuropathology report). No indentation of thecingulate gyri, unci or molding of the cerebellar tonsils are noted.

SPINAL CORD: The spinal cord is not removed.

PITUITARY GLAND: The pituitary gland is removed and is fixed in formalinfor subsequent examination by a neuropathologist.

BRAIN: Histologic examination of multiple sampled areas of the brainshowed the characteristic features of Creutzfetdt-Jakob disease. Thesewere present in most sections, but were particularly prominent in theoccipital cortex. The spongiform degeneration was seen in the neuropilof the gray matter as multiple vacuoles amoung numerous reactiveastrocytes and occasional neuronal cell bodies. These changes were mostnotable in the basal layer of the cortex. PAS and amyloid stains will beperformed on selected sections to asses the presence of plaques.

The clinical findings in this case strongly suggest the diagnosis ofCreutzfeldt-Jakob disease: progressive dementia, typical EEG changes,visual disturbances and myoclonus. These characteristics indicate thisis a "probable case of CJD", according the criteria set by the ECSurveillance Group of Creutzfeldt-Jakob Disease in Europe (1).The definitive diagnosis of Creutzfeldt-Jakob disease, however, isestablished by neuropathologic findings. There are three changes thatare classically described and considered diagnoseic: spongiform change,neuronal loss and astrocytic gliosis. The presence of these can varysignificantly in proportion and distribution and often correlate withclinical symptoms. This permits classification of the disease intoseveral variants.

Histological examination from multiple samples of the brain in this caserevealed astrocytic gliosis, spongiform degeneration and neuronal loss.Although these changes were seen in most sections, they were mostprominent in the occipital cortex. This correlates very well with theclinical history of visual disturbances. Based on this finding, thepresent case corresponds to the Heidenhain variant. It is not uncommonfor Creutzfeldt-Jakob disease to present with visual symptoms as theinitial manifestation of the disease. Vargas et al (3) has reportedthree cases with these characteristics.

There have been numerous and significant advances in our understandingof Creutzfeldt-Jakob disease and prion diseases in general. These havebeen reviewed in several papers written recently, including one byHorowich and Weissman (4).

In summary, this 63 year old female with a history of visualdisturbances and dementia of rapid progression was found to have theneuropathologic changes characteristic of Creutzfeldt-Jakob disease,predominantly in the occipital cortex. The occipital tropism andconsequent visual symptoms indicate this case corresponds to theHeidenhain variant.

Enclosed please find the microscopic slides and autopsy report from ourpatient, Barbara Poulter (Hosp.# 11851lQ, Autopsy # AU97-435). Theseslides are being sent for consultation at the request of Mr. Singletary,Ms. Poulter's son and next of kin. We will also send frozen tissue fromthe brain on dry ice next week, and someone will call you on the daythe tissue is shipped. Please return the slides when you have finishedwith your examination. If you need any further information, please donot hesitate to call me. Thanks for your assistance with this case.

Sincerely,Gerald A. Campbell------------------CASE WESTERN RESERVE UNIVERSITY

As per our telephone conversation concerning a recent case of CJD, IWill be willing to examine slides and the frozen tissue on westernblotting, I will issue a report to you about our conclusions. Below ismy address, Our Fed Ex number is XXXXXXXXXXXXXXX.

We are in receipt of the slides you sent on Mrs. Barbara Poulter (your#: AU97-435;our#098-28).

Best personal regards,Pierluigi Gambetti, M.D.

PG:sb

Division of NeuropathologyPierluigi Gambetti, M.D., Director-----------------------------------CASE WESTERN RESERVE UNIVERSITY

March 30, 1998

Dr. Gerald A, CampbellThe University of TexasMedical Branch at GalvestonDivision of NeuropathologyDepartment of PathologyGalveston, Texas

Dear Dr Campbell,

We performed Western immunoblot analysis on the frozen tissue from your case #AU97-435 (our #098-28). The Immunoblot reveals the presence ofprotease-resistant prion probein (PrPres) confirming the diagnosis of prion disease. The immunoblot pattern of PrPres is consistent with the diagnosis of Creutzfeldt-Jakob disease.

Thank you for referring to us this interesting case.

Sincerely,

Piero Parchi, M.D.

Pierluigi Gambetti, M.D.

PP:sb

Division of NeuropathologyPierluigi Gambetti, M.D., DirectorCase Western Reserve University

This Autopsy report is for the use of anyone, who is trying to understand this hideous disease CJD. I hope it can be benificial for some in researching human TSE. Please remember, this was my Mom, and to use this with great respect.

thank you,kind regards,

Terry S. Singeltary Sr., Bacliff, Texas USA

-------------------------------From: Jeff (webwizard.vegsource.org)Subject: Very interesting letter from son of CJD victim -- and alleged connection to cows

Date: April 22, 1998 at 19:53:42 EST

This was sent to Oprah Winfrey, reprinted here by permission:

I am the madson of a deadmom who died of madcow.(heidenhain variantcreutzfeldt-jacob disease.) I sat with her for 10 weeks and watched as this hidious disease ate her brain up. She wrote in her journal that she started to see brown spots on sept. 27, 1997. These were her first symptoms -- apprx.10 days later she was blind, about 2 weeks later she had lost control of her coordination, walking, and speech.

She would get these uncontrolable jerks that at times would take 3 of us to hold her down. Around the8th week she was totally bedridden. She died in the 10th week on 12-14-97. THANK GOD!

If you ever see this disease, as I did with my mom, you will truly believe that madcow is here. I truelybelieve that is what my mom died of. They can call it what ever they want to.

Now, I will take this a step further. My neighbor's mother also died of c.j.d. She died on 12-14-96, theyhad diagnosed it as Alzheimers, until the autopsy he demanded ruled out alzheimers and ruled in c.j.d.

About a month ago my neighbor called me over, he had been going through some old boxes of his mom'sand came across some pills he thought I should see. When I read the ingredients I just about sh*t!

INGREDIENTS: vacuum dried bovine brain, bone meal, bovine eye, veal bone, bovine liver powder,bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. It was a cow in a pill!This woman taking these pills died of c.j.d. Could it be madcow in a pill?

I called the texas dept. of health (T.D.H.) the next day, and the following day they were out here andgot the pills. I had located the manufacture and called with a bogus story and a list of doctors thatwould prescribe them in houston. The T.D.H. called a few days later, asking for the list of doctors, theirphone numbers, and told me they would take it from there. I need not persue it any further!

Not to long ago, 4 or 5 weeks, a girl showed up at my door. She had called crying a week earlier andcould not talk. She had seen a story on T.V. about my mother. Anyway, when I first saw her I knew shehad seen it too (madcow). Her mother had died of c.j.d. on 2-14-97.

This disease is here and you can call it what ever you want, c.j.d., n.v.c.j.d., hvCJD, b.s.e. or madcow, forwhat it is. But, that young man who died of n.v.c.j.d. in England, Steve Churchhill, had the exact samesymptoms as my mother. There is also a girl in Ft. Worth Texas who called me. She had seen an articleabout my mom in the dallas morning news. Her dad had died of c.j.d. so far we have come up with about18 people who has died of c.j.d. in texas, 15 confirmed. I have heard from other people its up to 32.

I am tired of hearing this crap about nv-cjd being in just young people. That same old line about hownv-cjd victims are much younger and their clinical course from first sign of symtoms to death is muchlonger. Any diseases clinical course is going to be longer in younger people, because their body andorgans are much younger and healthier. But, in the end, their brains are full of spongiform holes, just likethe older folks. Just because the plaques are more extreme, does not mean its a different disease. Couldit not be just a more extreme case of typical c.j.d.????

Greed is what it is all about. They banned feeding cattle to cattle. But, are still allowed to feed thosedowner cows to pork and poultry. Then they are still allowed to feed the pork and poultry byproductsback to the cows. Now Dr. Gibbs writes that the prion-protien can survive the digestinal track andcomposting process. So the prion-protein goes right back to the cow. We must ban feeding all animals to animals. Its just an endless cycle of greed thats killing people.

I have requested that further test be done on my moms brain.(frozen tissue, paraffeine sections andserum) be sent to case western reserve university in Cleveland, Ohio. Dr. Pierre Lugi Gambetti.

I hope you find some interest in this. I just don't believe we are being told everything. The gov. liedabout asbestos for 75 years.

P.S.-- the results from Case Western Reserve Universitiy, on my Mothers Brain, came back positive forthe prion protein PrPres, confirming the prion disease.........

INTRODUCTION: Creutzfeldt-Jakob's disease has various anatomoclinical presentations including a rare form with preponderant visual signs described by Heidenhain. In this form, the visual symptoms may be isolated for a few weeks, leading to multiple ophthalmological examinations. OBSERVATION: We report the case of a 75-year-old woman who developed isolated visual disorders which rapidly increased over a period of two months. Addition of neurological symptoms, abnormalities of EEG and positivity of 14-3-3 protein led to the diagnosis of Creutzfeldt-Jakob's disease. The patient died 14 months after the first neuroophthalmologic signs. The diagnosis was established by post-mortem examination and immuno-electrophoretic demonstration of type 1 prion protein. CONCLUSION: Heidenhain's form of Creutzfeldt-Jakob's disease highlights the importance of general rules for prevention of iatrogenic hazard during ophthalmological examinations.

ABSTRACT Background: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD).

Methods: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1).

Results: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues.

Conclusions: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.

HARD telling how many people my mother exposed with all the exams she had during her first symptoms of blindness while being examinded with many different optical equipment, during her short course of clinical disease that being from onset of symptoms to death approx. 10 weeks. ...